Several research projects in this proposal focus on environmental pollutants that bind to specific protein receptors and impact regulatory pathways, resulting in developmental and reproductive abnormalities. In agreement with the research tools that are applicable to most projects in the proposal, the Bioinformatics and Molecular Modeling Research Support Core will provide computational tools, expertise, and help in two areas: modeling of interactions between xenobiotics and protein receptors using methods of structural bioinformatics and computational biology;and the analysis of gene expression data, including the reconstruction of regulatory pathways. The particular functions of the core include (1) developing and providing computational methods to address specific needs for the modeling of 3D structures of nuclear receptors and P450s, and their interactions with xenobiotics;(2) developing a database of the interactions between environmental chemicals and relevant protein receptors;(3) providing assistance in the analyses of microarray data, including the reconstruction of regulatory pathways affected by xenobiotics binding, and (4) collaborating with the Pis on the individual projects. Experience from the preceding performance period shows that integration of experimental and computational approaches to the analysis of the molecular mechanisms of xenobiotics-receptor interactions goes beyond consulting and providing resources, and that interdisciplinary research requires continued scientific involvement of the Core personnel, including some method development. While the analysis of gene expression data includes some routine operations, interpretation of the data and the mapping of results into regulatory pathways will also require similar integration of experimental, theoretical, and computational approaches. Therefore, the Personnel of the Core will actively participate in the research projects that use structural modeling and/or microarray techniques.